Amyloid-like deposits in the brain of transgenic mice overexpressing S100B protein.

Abstract

S100 calcium-binding protein B (S100B) is a member of the S100 family, mainly expressed and secreted by astrocytes in the Central Nervous System. Extracellular levels of this protein have been used as a general marker of brain injury, particularly in blood serum and cerebrospinal fluid (CSF). Mice overexpressing S100B (S100BTg) was firstly developed to better understand the Down Syndrome and Alzheimer's Disease, once both S100B and amyloid precursor protein (APP) genes are located in chromosome 21. Also, it was previously demonstrated the exacerbation of amyloidogenesis in transgenic mice for both human APP and S100B, but the influence of this protein on APP processing had not yet been investigated in the S100BTg itself. Considering the interaction between the S100B protein and the amyloid beta processing, as well as the S100B's neuroinflammatory signalling, we investigated S100B and amyloid beta 42 peptide levels by Elisa in the hippocampus (Hp), frontal cortex (FC), hypothalamus (Ht), CSF, serum and also the possible amyloid deposition by Thioflavin-T and immunofluorescence in 1-year-old transgenic mice overexpressing S100B as Reeves' procedure, in female and male S100BTg and respective wild type (Wt) mice. Our results showed a higher S100B content in the three examined brain regions of S100BTg (Hp, FC and Ht) and Hp showed higher levels of this protein than other two regions, even in Wt. Moreover, for the first time we found elevated CSF S100B in these old transgenic mice, which supports the idea that S100B released by astrocytes could affect the neural neighborhood. In addition, we found more plaque-like deposits in males S100Tg than females in comparison with Wt. Ultimately, our data reinforces the importance and potential of this model for experimental studies and the role of S100B in the pathogenesis of AD, points out specific brain changes of S100B (in brain tissue and CSF) and indicates that changes in S100B and amyloid plaques in this mice seems to be dependent on sex.